From the National Cancer Institute, National Institutes of Health, Bethesda, MD; and the Washington Cancer Institute, Washington Hospital Center, Washington, DC
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Sandra M. Swain, MD, Medical Director, Washington Cancer Institute, Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010; e-mail: Sandra.M.Swain{at}Medstar.net
Overview: Trastuzumab, in combination with cytotoxic chemotherapy in the adjuvant setting, improves both disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. Lapatinib, a dual tyrosine kinase inhibitor of HER-1 and HER-2 has proven efficacy in the metastatic setting when combined with capecitabine in patients previously treated with trastuzumab; however, its role in the adjuvant setting needs to be defined. Not all patients with HER-2-positive breast cancer respond to trastuzumab, and many will develop resistance to this therapy. Elucidating strategies to overcome resistance to HER-2 targeting agents is an important step in optimizing the treatment of HER-2-positive breast cancer. Vascular endothelial growth factor (VEGF), an important mediator of angiogenesis, has been shown to be upregulated in HER-2-positive breast cancer supporting the rationale for combining HER-2 targeting agents with the monoclonal antibody bevacizumab. The combination of bevacizumab and taxanes in the metastatic setting resulted in significant improvement in disease-free survival. Clinical trials to define the utility of anti-VEGF treatment in the adjuvant setting are ongoing. The combination of anti-HER-2 and antiangiogenic agents, as well as those agents that target the downstream HER-2 signaling pathway, are areas of active research that may prove to be effective strategies for improving targeted treatment in breast cancer.
